The present invention relates generally to a tubular implantable prosthesis for the delivery of a bioactive material. More particularly, the present invention relates to a multi-layered tubular endoprosthesis formed of a combination of expanded polytetrafluoroethylene, and a tubular, diametrically-deformable stent.
It is known to use extruded tubes of polytetrafluoroethylene (PTFE) as implantable intraluminal prosthesis, particularly vascular grafts, stents, and stent/graft composites. PTFE is particularly suitable as an implantable prosthesis due to its biocompatibility. PTFE tubes may be used as vascular grafts in the replacement or repair of blood vessels. In vascular applications, the grafts, stents, and stent/graft composites are manufactured from expanded polytetrafluoroethylene (ePTFE) tubes. Extruded PTFE tubes having minimal wall thickness are described in commonly owned, copending application Ser. No. 10/012,919. An apparatus and method for extrusion of thin-walled PTFE tubes are described in commonly owned, copending application Ser. No. 10/012,825.
Grafts formed of ePTFE have a fibrous state which is characterized by lengthwise-oriented fibrils interrupted by transverse nodes, the fibrous state being formed during the process of stretching and expanding the PTFE. The space between the node surfaces that is spanned by the fibrils is defined as the internodal distance (IND). Nodes and fibrils may be further characterized in terms of their relative geometry. In particular, nodes can be characterized by length, width, and height; and fibrils, by diameter and length. It is the relative geometry of nodes to fibrils, as well as the internodal distance that determines the porosity and permeability of porous PTFE.
The porosity of an ePTFE vascular graft may be tailored to achieve desirable properties in the structures of nodes and fibrils that affect cell permeability and tissue in-growth. For example, by controlling the conditions under which PTFE is stretched and expanded, the IND of the microporous structure of the tube can be varied. It is known that a graft having a large IND, for example, greater than 30 microns, results in enhanced tissue growth as well as cell endothelization as a result of the graft being inherently more porous. However, such an increase in the porosity of the tubular structure also results in a reduction in the overall radial tensile strength of the tube as well as a reduction in the ability of the graft to retain a suture placed during implantation. In addition, microporous tubular structures having a large IND tend to exhibit low axial tear strength, so that a small tear or nick will tend to propagate along the length of the tube.
Attempts to increase the radial tensile and axial tear strengths of microporous ePTFE tubes include forming the tubular grafts of multiple layers placed over one another. Examples of multi-layered ePTFE tubular structures useful as implantable prosthesis are shown in U.S. Pat. Nos. 4,816,339; 4,478,898; 5,001,276; 5,800,512; 5,749,880; 5,810,870; and 5,824,050.
It is further known to provide a tubular vascular graft of ePTFE with layers sufficient to provide a differential cross-section of permeability and/or porosity to achieve enhanced healing and tissue in-growth. For example, U.S. Pat. No. 5,800,512 describes a multi-layered ePTFE composite tubular structure including a tissue contacting expanded outer tube and a concentrically adjacent expanded inner tube, an inner surface of which is a blood contacting surface. The graft has an inner tube with an IND of greater than 40 microns which promotes cell endothelization along the inner surface and an outer tube of ePTFE having an IND of less than 40 microns which exhibits an increased radial strength relative to the inner tube. A middle layer of ePTFE of low IND may be interposed for increasing the radial strength of the resultant composite graft. Alternately, a middle layer of high IND may be interposed for increasing the porosity of the composite structure for further promoting cell endothelization and/or tissue in-growth.
Moreover, U.S. Pat. No. 5,824,050 discloses a multi-layered tubular graft, which may be formed of layers of ePTFE, having different porosities. A three layer graft includes three cross-section regions wherein the IND of the pores of the luminal surface of the graft is about 20 or 30 microns and the tissue contacting surface of the graft has a pore size range of 50 to 500 microns. A middle layer of low IND modulates cellular penetration between the outer and inner layers, while allowing the transport of plasma solutes between the outer and inner layers. The barrier middle layer minimizes the relatively large hydraulic force present in arterial transport that retards tissue growth. A disadvantage of this tubular graft is that the outer layer, because of its large IND, exhibits a decreased radial strength. Thus, this graft may not be suitable for use in combination with an expandable device, such as a balloon-expandable stent.
It is also known to incorporate therapeutic agents into implantable ePTFE materials. The use of therapeutic agents in ePTFE prosthetics is desirable to prevent various complications which may arise as a result of implantation of the prosthetic and to promote cell endothelization, tissue in-growth and healing. Such therapeutic agents can be provided in the ePTFE material as a dispersion in a biocompatible, biodegradable material. Various pharmacological active agents, such as antimicrobials, antivirals, antibiotics, growth factors, and blood clotting modulators, such as heparin, can be added to the material such that these agents are introduced into the body as the material is bioresorbed. For example, U.S. Pat. No. 5,665,114 to Weadock et al. discloses an implantable ePTFE prosthesis which incorporates a biocompatible, biodegradable material of natural origin.
U.S. Pat. No. 5,411,550 also describes an implantable prosthetic device for delivering a bioactive material into a blood vessel of a patient. The device including a single tubular body of ePTFE extruded as a continuous wall, the wall having at least a primary and secondary lumen, wherein the secondary lumen receives the bioactive material. A disadvantage of this device is that because the tubular body is extruded as a single continuous wall, it is not possible to provide a luminal surface and a tissue contacting surface with distinct porosities.
There is, therefore, a need to provide ePTFE multi-layered tubular grafts and stent/graft configurations which exhibit increased porosity, desirably at the inner surface thereof, while retaining a high degree of radial strength, desirably at the external surface thereof and which provide for regulated delivery of therapeutic agents incorporated therein or thereon to a site of implantation of the device. In particular, it is desirable to provide an ePTFE vascular graft and stent/graft configuration which includes a mechanism for regulating the transport of substances between surfaces of the prosthesis with a high degree of specificity.
The present invention provides for an implantable composite device for regulating delivery of bioactive agents associated therewith to a site of implantation of the device including: (a) a luminal zone of first porosity; and (b) a second zone of second porosity circumscribing the luminal zone, the second zone permitting regulated transport of natural or synthetic bioactive agents therethrough.
The invention further provides for an implantable composite device for regulating delivery of bioactive agents associated therewith to a site of implantation of the device including (a) a first luminal layer of ePTFE having a first porosity sufficient to promote cell endothelization therealong; and (b) a second polymeric layer disposed on the first layer, the second layer having a second porosity permitting regulated transport of natural or synthetic bioactive therapeutic agents therethrough.
In one embodiment of the present invention, the implantable composite device for regulating delivery of bioactive agents associated therewith to a site of implantation of the device includes: (a) a first luminal layer of ePTFE having pores of an internodal distance of greater than 40 microns and (b) a second layer disposed on the first layer, the second layer having a porosity defined by an internodal distance of about 5-10 microns and a specific node/fibril geometry of about 5 to about 10 microns, the second layer permitting regulated transport of natural or synthetic bioactive therapeutic agents therethrough.
In a further embodiment, the implantable composite device for regulating delivery of bioactive agents associated therewith to a site of implantation of the device includes: (a) a first luminal layer of ePTFE having pores of an internodal distance of less than 40 microns and (b) a second layer of ePTFE disposed on the first layer, the second layer having a porosity defined by an internodal distance of about 5-10 microns and a specific node/fibril geometry of about 5 to about 10 microns, the second layer permitting regulated transport of natural or synthetic bioactive therapeutic agents therethrough.
In another aspect of the invention there is provided a method of making an implantable composite device for regulating delivery of bioactive agents associated therewith to a site of implantation of the device, the method including: (a) providing a first luminal layer of ePTFE material of a first porosity and (b) disposing a second layer of a natural or synthetic polymeric material of a second porosity onto the first layer, the second layer permitting regulated transport of natural or synthetic bioactive agents therethrough.
Furthermore, a method for treating a lumen in a body is provided, the method including the steps of: (a) inserting an implantable composite device for regulating delivery of bioactive agents associated therewith into said lumen, the device including : (i) a luminal zone of first porosity; and (ii) a second zone of second porosity circumscribing the luminal zone, the second zone permitting regulated transport of natural or synthetic bioactive agents therethrough; and (b) fixing said implantable composite device to said lumen such that it will stay where positioned.